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Biomedical subjects

H Cooper

Publications and source records attributed to H Cooper.

At least 37 records · Page 2Linked to original sources

Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H.

Patients with severe rheumatoid arthritis who had failed treatment with conventional therapies were treated with a course of five or 10 daily intravenous infusions of CAMPATH-1H, a humanized antibody against the CD52 antigen, resulting in profound depletion of peripheral blood mononuclear cells. During the subsequent 18 months, lymphocytes were analysed for sub-populations by fluorescence-activated cell sorter (FACS) and for proliferation in response to polyclonal T-cell stimulation with anti-CD3 or staphylococcal enterotoxin B (SEB). Treatment resulted in almost complete depletion of lymphocytes from the blood followed by gradual repopulation. CD16+ natural killer (NK) cells and CD14+ monocytes returned to pretreatment levels within 1-2 months. CD19+ B cells returned to within 50% of pre-treatment levels by day 66 and to within normal range by day 150, whereas CD8+ T cells recovered to 50% of pretreatment levels by day 66, but did not show any further increase during the rest of the study period. The most profound effects were on the CD4+ T lymphocyte sub-population, as the mean CD4+ count did not increase above 20% of pre-treatment level at any time during the study period (550 days), at all the doses tested. The T cells which initially repopulated the blood 1-2 months after treatment, nearly all expressed the activation markers human leucocyte antigen (HLA)-DR and CD45RO, although the percentage of T cells expressing these molecules gradually declined to normal levels over time. Proliferative responses to polyclonal T-cell stimulation (anti-CD3 and SEB) were also significantly reduced in the first few months after treatment, but recovered to pre-treatment levels by day 250. The relationship between these observations and the clinical response is discussed.

Antibodies, Monoclonal↗

Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment.

CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expressed at high levels on normal T and B lymphocytes and at lower levels on monocytes, while being absent on granulocytes and bone marrow stem cell precursors. The emergence of CD52- lymphocytes of both T and B cell lineages was observed in three out of 25 rheumatoid arthritis patients treated with teh humanized antibody Campath-1H in phase II clinical trial. Whereas the majority of CD52- B cells had disappeared from the peripheral blood by 3 months post-treatment, both CD52- CD4+ and CD8+ T cells persisted in the circulation for at least 20 months. In the two patients that were tested, the GPI-anchored surface molecules CD55 and CD59 were also absent on the CD52- cells, although expression of other cell surface transmembrane, proteins (CD3, CD4 and CD2) was unaffected. The CD52- cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture. Both CD52- and C52+ clones, established from one of the patients, responded to a similar extent to several T cell mitogens, as assessed by proliferation, suggesting that a general defect in expression of GPI-linked molecules does not impair T cell activation. These data show that an immune attack against a GPI-anchored surface molecule can result in the selection of a GPI-anchor-deficient cell population. Despite the persistence of CD52- T cells in the peripheral blood, no adverse reactions associated with the presence of these cells were noted in any of the patients; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.

Adult↗

Reported benefits and problems experienced with bone-anchored hearing aids.

Within this study we have examined the self-reported benefits and shortcomings experienced by patients fitted with bone-anchored hearing aids using an open-ended approach developed for hearing aid users. Reports were obtained from 39 patients who, between them, listed 165 benefits and 105 shortcomings. Benefits and shortcomings could be sub-divided into four main groups: practical, acoustical, psychological and medical, in that order of frequency. The most commonly reported benefits included hearing better and clearer, ease of use, inconspicuousness, and the fact that it made the individual more confident. The main shortcomings were difficulties with the telephone, wind noise and hearing speech in noise.

Acoustics↗

Barriers to screening and counseling pregnant women for alcohol use.

The consequences of fetal alcohol exposure are far-reaching and preventable. Health care providers are uniquely positioned to promote alcohol-free pregnancy, yet an array of factors inhibit routine screening, counseling, and referral. This descriptive, qualitative study explored experiences and perceived barriers related to prenatal screening for alcohol use. The study included eight focus groups (71 participants) and 41 key informant interviews with health care professionals representing a mix of disciplines. Nearly 40% of the providers were physicians who regularly encounter women in their practices. While most providers ask about alcohol use, few probe in depth or follow up. The findings should alert program planners and medical educators to strengthen their preventive medical and public health practices.

Adolescent↗

Detection of rare allelic variants of the interferon-alpha 2 gene in human genomic DNA.

We have analyzed human donor DNA for the presence of sequences corresponding to allelic variants of the IFN-alpha 2 locus. Using both restriction enzyme digestion of PCR-amplified fragments and sequence analysis of these fragments, we have identified the three reported allelic variants, IFN-alpha 2a, IFN-alpha 2b, and IFN-alpha 2c, in genomic DNA derived from donors of African or Afro-Caribbean origin. This is the first report of the IFN-alpha 2a and IFN-alpha 2c alleles occurring in human donor DNA and supports the view that these are variants of the predominant IFN-alpha 2b allele rather than arising from mutations occurring in cultured cells.

Alleles↗

Patient education for sickle cell disease: a national survey of health care professionals.

Despite emphasis on including patient and parent education in sickle cell comprehensive clinical care, literature on the use of such materials is scarce. To discover the availability of, satisfaction with, use of and interest in patient and parent education materials for sickle cell disease, we surveyed, with a 176-item self-administered questionnaire, 209 sickle cell professionals nationwide. Respondents came from 74 sickle cell programs, were 63.4% female and 37.7% African American, and represented many health professions. We found that materials about patient behavior and psycho-social issues, as opposed to those about the disease and treatment, were more often unavailable and, when available, more often unsatisfactory and less frequently used. When available, use of materials was unrelated to satisfaction and perceptions of patient problems for most topics. For each of 10 topics, over 90% of the respondents were interested in materials covering the topic. Future research should examine the low to moderate use of psycho-social and behavioral materials with sickle cell patients, and should assess the appropriateness and effectiveness of existing and new materials.

Adult↗

Homework for students with learning disabilities: the implications of research for policy and practice.

The literature on homework for students with learning disabilities is reviewed. First, a summary of Cooper's (1989a) synthesis of research on homework for students without disabilities is presented, including (a) a definition of homework, (b) a model of the homework process, (c) the results of a meta-analysis of homework studies, and (d) generic policy guidelines. Next, special education research on homework conducted after 1985 is described. The literature is divided into studies that manipulated homework conditions and homework-related surveys of teachers and parents. The results of the literature review suggest that homework policies and practices for students with learning disabilities should emphasize (a) simple, short assignments; (b) careful monitoring by and prominent rewards from teachers; and (c) parental involvement, especially to provide structure, conducive environments, and immediate rewards.

Adolescent↗

Comparison of expression of a humanized monoclonal antibody in mouse NSO myeloma cells and Chinese hamster ovary cells.

We report a detailed comparison of two commonly used stable, amplifiable mammalian expression systems (Chinese Hamster Ovary cells/dihydrofolate reductase and Mouse NSO myeloma/glutamine synthetase) used to express a humanized IgG1 monoclonal antibody. We compare copy number and steady state mRNA levels of both the selectable marker and heavy chain of the antibody throughout the selection and amplification process. In both cell lines, copy number and steady state levels of heavy chain and selectable marker increased during selection and were further increased during amplification. As expected, an increase in steady state mRNA levels of heavy chain correlated with an increase in expression of antibody whilst an increase in the steady state levels of mRNA of the selectable marker correlated with increased resistance to the selective agent. In NSO and CHO cells producing equivalent amounts of antibody, the copy number of the antibody genes and selectable marker was significantly higher in the CHO cells than in the NSO cells. However, the steady state mRNA levels of the heavy chain of the antibody were virtually identical. Rates of protein secretion in the two cell lines were also compared and found to be very similar. When the antibody purified from both systems was compared in a number of functional assays they behaved identically.

Animals↗

Retinal projection to the olfactory tubercle and basal telencephalon in primates.

The retinal projection to the basal telencephalon was studied in eight species of primates from the suborders Strepsirhini and Haplorhini, including one anthropoid primate, the gibbon. Animals received an intraocular injection of tritiated amino acids and the distribution of retinal fibers and terminals was demonstrated by autoradiographic techniques in horizontal and coronal sections. In all species a discrete group of labeled retinal fibers is observed to branch off from the dorsolateral aspect of the optic tract at the level of the suprachiasmatic nucleus. These fibers, destined to the basal telencephalon, are topographically distinct from the retinal fibers which innervate the suprachiasmatic nucleus and medial hypothalamic regions. The fibers of the retinotelencephalic tract course dorsally above the supraoptic nucleus through the lateral hypothalamic area and then proceed further rostrally and laterally below the diagonal band of Broca towards the olfactory tubercle. Within the olfactory tubercle, terminal distribution of label is observed in the mediocaudal region along the granular cell layer II. In the macaque this cellular layer shows a characteristic thickening in the region of retinal terminals which is evident in both coronal and horizontal section. In some species this labeled region is seen within the superficial bulge of the tubercle on the ventral aspect of basal telencephalon. In all primates the retinal projection to olfactory tubercle is bilateral. In prosimians label is predominantly contralateral to the injected eye, in New World monkeys label is equally distributed on both sides of the brain and in Old World monkeys label is mainly found ipsilaterally. Retinal fibers were also seen in the periamygdaloid region but never extended as far as piriform cortex. These results, in addition to previous studies in other mammalian orders, confirm that the basal telencephalon, and in particular the olfactory tubercle, constitutes a region of visual and olfactory convergence. This sensory integration may be related to photic and chemosensory modulation of reproductive physiology and behavior.

Animals↗

Immunogenicity of a hybrid Plasmodium falciparum malaria antigen.

A recombinant baculovirus-expressed hybrid protein containing epitopes for the C-terminal fragment of the Plasmodium falciparum precursor to the major merozoite surface antigens (PMMSA) and the tetrapeptide repeats of the circumsporozoite protein (CSP) was assessed for its immunogenicity. Murine MHC-II restriction of the antibody response to the CSP repeats was not overcome by the PMMSA component, the response to which showed no restriction. In an adjuvant trial the highest antibody titres in rabbits to both components of the hybrid were obtained using Freund's adjuvant. Lack of a boosting antibody response to the CSP repeats appeared to be linked to the conformation of the PMMSA component. Formulation of the hybrid protein into Iscoms gave antibody titres of only short duration to both components.

Adjuvants, Immunologic↗

Analysis of interferon-alpha 2 sequences in human genomic DNA.

We have analyzed the genomic DNA sequence corresponding to the human interferon-alpha 2 (IFN-alpha 2) gene locus. In human lymphoblastoid Namalwa cells, we have detected sequences corresponding to IFN-alpha 2b and -2c, while in human KG-1 cells both IFN-alpha 2a and -2b were present. However, in 100 independent IFN-alpha 2 clones derived from 20 unrelated Caucasian volunteers, we found only sequences corresponding to IFN-alpha 2b. Statistical analysis of this result suggests that the sequences corresponding to IFN-alpha 2a and -2c are either rare allelic variants of this gene, occurring in only a minority of the Caucasian population, or are restricted to transformed cell lines.

Amino Acid Sequence↗

Root canal treatment on patients with HIV infection.

Patients attending a dedicated dental clinic during the previous 24 months were assessed for the success of root canal treatment. Two groups, totalling 48 patients, had root canal treatment to 57 teeth performed by one operator. All treatment was carried out without antibiotic prophylaxis over two or more appointments. Patients with HIV infection had root canal treatment to 40 teeth. Sixteen patients in the control group had root canal treatment to 17 teeth. Short-term success was determined by follow-up appointments 1-3 months following obturation. No complications were experienced in either group, except with one HIV infected patient. The results of this clinical study indicate that root canal treatment can be carried out following standard procedures and without antibiotic prophylaxis.

Adult↗